Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein-Based Vaccine Adjuvanted With Glucopyranosyl Lipid A-Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge.

Autor:	Friedman-Klabanoff DJ; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA., Berry AA; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA., Travassos MA; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA., Shriver M; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA., Cox C; The Emmes Company, Rockville, Maryland, USA., Butts J; The Emmes Company, Rockville, Maryland, USA., Lundeen JS; The Emmes Company, Rockville, Maryland, USA., Strauss KA; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA., Joshi S; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA., Shrestha B; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA., Mo AX; Parasitology and International Programs Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Nomicos EYH; Parasitology and International Programs Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Deye GA; Parasitology and International Programs Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Regules JA; Biologics Research & Development, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Bergmann-Leitner ES; Biologics Research & Development, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Pasetti MF; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA., Laurens MB; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 Jun 14; Vol. 229 (6), pp. 1883-1893.
DOI:	10.1093/infdis/jiae062
Abstrakt:	Background: Malaria is preventable yet causes >600 000 deaths annually. RTS,S, the first marketed malaria vaccine, has modest efficacy, but improvements are needed for eradication. Methods: We conducted an open-label, dose escalation phase 1 study of a full-length recombinant circumsporozoite protein vaccine (rCSP) administered with adjuvant glucopyranosyl lipid A-liposome Quillaja saponaria 21 formulation (GLA-LSQ) on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naive adults. The primary end points were safety and reactogenicity. The secondary end points were antibody responses and Plasmodium falciparum parasitemia after homologous controlled human malaria infection. Results: Participants were enrolled into 4 groups receiving rCSP/GLA-LSQ: 10 µg × 3 (n = 20), 30 µg × 3 (n = 10), 60 µg × 3 (n = 10), or 60 µg × 2 (n = 9); 10 participants received 30 µg rCSP alone × 3, and there were 6 infectivity controls. Participants experienced no serious adverse events. Rates of solicited and unsolicited adverse events were similar among groups. All 26 participants who underwent controlled human malaria infection 28 days after final vaccinations developed malaria. Increasing vaccine doses induced higher immunoglobulin G titers but did not achieve previously established RTS,S benchmarks. Conclusions: rCSP/GLA-LSQ had favorable safety results. However, tested regimens did not induce protective immunity. Further investigation could assess whether adjuvant or schedule adjustments improve efficacy. Clinical Trials Registration: NCT03589794. Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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